Tag Archives: FDA

Killing bacteria on contact with dragonfly-inspired nanocoating

Scientists in Singapore were inspired by dragonflies and cicadas according to a March 28, 2018 news item on Nanowerk (Note: A link has been removed),

Studies have shown that the wings of dragonflies and cicadas prevent bacterial growth due to their natural structure. The surfaces of their wings are covered in nanopillars making them look like a bed of nails. When bacteria come into contact with these surfaces, their cell membranes get ripped apart immediately and they are killed. This inspired researchers from the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR to invent an anti-bacterial nano coating for disinfecting frequently touched surfaces such as door handles, tables and lift buttons.

This technology will prove particularly useful in creating bacteria-free surfaces in places like hospitals and clinics, where sterilization is important to help control the spread of infections. Their new research was recently published in the journal Small (“ZnO Nanopillar Coated Surfaces with Substrate-Dependent Superbactericidal Property”)

Image 1: Zinc oxide nanopillars that looked like a bed of nails can kill a broad range of germs when used as a coating on frequently-touched surfaces. Courtesy: A*STAR

A March 28, 2018 Agency for Science Technology and Research (A*STAR) press release, which originated the news item, describes the work further,

80% of common infections are spread by hands, according to the B.C. [province of Canada] Centre for Disease Control1. Disinfecting commonly touched surfaces helps to reduce the spread of harmful germs by our hands, but would require manual and repeated disinfection because germs grow rapidly. Current disinfectants may also contain chemicals like triclosan which are not recognized as safe and effective 2, and may lead to bacterial resistance and environmental contamination if used extensively.

“There is an urgent need for a better way to disinfect surfaces without causing bacterial resistance or harm to the environment. This will help us to prevent the transmission of infectious diseases from contact with surfaces,” said IBN Executive Director Professor Jackie Y. Ying.

To tackle this problem, a team of researchers led by IBN Group Leader Dr Yugen Zhang created a novel nano coating that can spontaneously kill bacteria upon contact. Inspired by studies on dragonflies and cicadas, the IBN scientists grew nanopilllars of zinc oxide, a compound known for its anti-bacterial and non-toxic properties. The zinc oxide nanopillars can kill a broad range of germs like E. coli and S. aureus that are commonly transmitted from surface contact.

Tests on ceramic, glass, titanium and zinc surfaces showed that the coating effectively killed up to 99.9% of germs found on the surfaces. As the bacteria are killed mechanically rather than chemically, the use of the nano coating would not contribute to environmental pollution. Also, the bacteria will not be able to develop resistance as they are completely destroyed when their cell walls are pierced by the nanopillars upon contact.

Further studies revealed that the nano coating demonstrated the best bacteria killing power when it is applied on zinc surfaces, compared with other surfaces. This is because the zinc oxide nanopillars catalyzed the release of superoxides (or reactive oxygen species), which could even kill nearby free floating bacteria that were not in direct contact with the surface. This super bacteria killing power from the combination of nanopillars and zinc broadens the scope of applications of the coating beyond hard surfaces.

Subsequently, the researchers studied the effect of placing a piece of zinc that had been coated with zinc oxide nanopillars into water containing E. coli. All the bacteria were killed, suggesting that this material could potentially be used for water purification.

Dr Zhang said, “Our nano coating is designed to disinfect surfaces in a novel yet practical way. This study demonstrated that our coating can effectively kill germs on different types of surfaces, and also in water. We were also able to achieve super bacteria killing power when the coating was used on zinc surfaces because of its dual mechanism of action. We hope to use this technology to create bacteria-free surfaces in a safe, inexpensive and effective manner, especially in places where germs tend to accumulate.”

IBN has recently received a grant from the National Research Foundation, Prime Minister’s Office, Singapore, under its Competitive Research Programme to further develop this coating technology in collaboration with Tan Tock Seng Hospital for commercial application over the next 5 years.

1 B.C. Centre for Disease Control

2 U.S. Food & Drug Administration

(I wasn’t expecting to see a reference to my home province [BC Centre for Disease Control].) Back to the usual, here’s a link to and a citation for the paper,

ZnO Nanopillar Coated Surfaces with Substrate‐Dependent Superbactericidal Property by Guangshun Yi, Yuan Yuan, Xiukai Li, Yugen Zhang. Small https://doi.org/10.1002/smll.201703159 First published: 22 February 2018

This paper is behind a paywall.

One final comment, this research reminds me of research into simulating shark skin because that too has bacteria-killing nanostructures. My latest about the sharkskin research is a Sept, 18, 2014 posting.

Sunscreens: 2018 update

I don’t usually concern myself with SPF numbers on sunscreens as my primary focus has been on the inclusion of nanoscale metal particles (these are still considered safe). However, a recent conversation with a dental hygienist and coincidentally tripping across a June 19, 2018 posting on the blog shortly after the convo. has me reassessing my take on SPF numbers (Note: Links have been removed),

So, what’s the deal with SPF? A recent interview of Dr Steven Q Wang, M.D., chair of The Skin Cancer Foundation Photobiology Committee, finally will give us some clarity. Apparently, the SPF number, be it 15, 30, or 50, refers to the amount of UVB protection that that sunscreen provides. Rather than comparing the SPFs to each other, like we all do at the store, SPF is a reflection of the length of time it would take for the Sun’s UVB radiation to redden your skin (used exactly as directed), versus if you didn’t apply any sunscreen at all. In ideal situations (in lab settings), if you wore SPF 30, it would take 30 times longer for you to get a sunburn than if you didn’t wear any sunscreen.

What’s more, SPF 30 is not nearly half the strength of SPF 50. Rather, SPF 30 allows 3% of UVB rays to hit your skin, and SPF 50 allows about 2% of UVB rays to hit your skin. Now before you say that that is just one measly percent, it actually is much more. According to Dr Steven Q. Wang, SPF 30 allows around 1.5 times more UV radiation onto your skin than SPF 50. That’s an actual 150% difference [according to Wang’s article “… SPF 30 is allowing 50 percent more UV radiation onto your skin.”] in protection.

(author of the ‘eponymous’ blog) offers a good overview of the topic in a friendly, informative fashion albeit I found the ‘percentage’ to be a bit confusing. (S)he also provides a link to a previous posting about the ingredients in sunscreens (I do have one point of disagreement with regarding oxybenzone) as well as links to Dr. Steven Q. Wang’s May 24, 2018 Ask the Expert article about sunscreens and SPF numbers on skincancer.org. You can find the percentage under the ‘What Does the SPF Number Mean?’ subsection, in the second paragraph.

Ingredients: metallic nanoparticles and oxybenzone

The use of metallic nanoparticles  (usually zinc oxide and/or (titanium dioxide) in sunscreens was loathed by civil society groups, in particular Friends of the Earth (FOE) who campaigned relentlessly against their use in sunscreens. The nadir for FOE was in February 2012 when the Australian government published a survey showing that 13% of the respondents were not using any sunscreens due to their fear of nanoparticles. For those who don’t know, Australia has the highest rate of skin cancer in the world. (You can read about the debacle in my Feb. 9, 2012 posting.)

At the time, the only civil society group which supported the use of metallic nanoparticles in sunscreens was the Environmental Working Group (EWG).  After an examination of the research they, to their own surprise, came out in favour (grudgingly) of metallic nanoparticles. (The EWG were more concerned about the use of oxybenzone in sunscreens.)

Over time, the EWG’s perspective has been adopted by other groups to the point where sunscreens with metallic nanoparticles are commonplace in ‘natural’ or ‘organic’ sunscreens.

As for oxybenzones, in a May 23, 2018 posting about sunscreen ingredients notes this (Note: Links have been removed),

Oxybenzone – Chemical sunscreen, protects from UV damage. Oxybenzone belongs to the chemical family Benzophenone, which are persistent (difficult to get rid of), bioaccumulative (builds up in your body over time), and toxic, or PBT [or: Persistent, bioaccumulative and toxic substances (PBTs)]. They are a possible carcinogen (cancer-causing agent), endocrine disrupter; however, this is debatable. Also could cause developmental and reproductive toxicity, could cause organ system toxicity, as well as could cause irritation and potentially toxic to the environment.

It seems that the tide is turning against the use of oxybenzones (from a July 3, 2018 article by Adam Bluestein for Fast Company; Note: Links have been removed),

On July 3 [2018], Hawaii’s Governor, David Ig, will sign into law the first statewide ban on the sale of sunscreens containing chemicals that scientists say are damaging the Earth’s coral reefs. Passed by state legislators on May 1 [2018], the bill targets two chemicals, oxybenzone and octinoxate, which are found in thousands of sunscreens and other skincare products. Studies published over the past 10 years have found that these UV-filtering chemicals–called benzophenones–are highly toxic to juvenile corals and other marine life and contribute to the fatal bleaching of coral reefs (along with global warming and runoff pollutants from land). (A 2008 study by European researchers estimated that 4,000 to 6,000 tons of sunblock accumulates in coral reefs every year.) Also, though both substances are FDA-approved for use in sunscreens, the nonprofit Environmental Working Group notes numerous studies linking oxybenzone to hormone disruption and cell damage that may lead to skin cancer. In its 2018 annual sunscreen guide, the EWG found oxybenzone in two-thirds of the 650 products it reviewed.

The Hawaii ban won’t take effect until January 2021, but it’s already causing a wave of disruption that’s affecting sunscreen manufacturers, retailers, and the medical community.

For starters, several other municipalities have already or could soon join Hawaii’s effort. In May [2018], the Caribbean island of Bonaire announced a ban on chemicals sunscreens, and nonprofits such as the Sierra Club and Surfrider Foundation, along with dive industry and certain resort groups, are urging legislation to stop sunscreen pollution in California, Colorado, Florida, and the U.S. Virgin Islands. Marine nature reserves in Mexico already prohibit oxybenzone-containing sunscreens, and the U.S. National Park Service website for South Florida, Hawaii, U.S. Virgin Islands, and American Samoa recommends the use of “reef safe” sunscreens, which use natural mineral ingredients–zinc oxide or titanium oxide–to protect skin.

Makers of “eco,” “organic,” and “natural” sunscreens that already meet the new standards are seizing on the news from Hawaii to boost their visibility among the islands’ tourists–and to expand their footprint on the shelves of mainland retailers. This past spring, for example, Miami-based Raw Elements partnered with Hawaiian Airlines, Honolulu’s Waikiki Aquarium, the Aqua-Aston hotel group (Hawaii’s largest), and the Sheraton Maui Resort & Spa to get samples of its reef-safe zinc-oxide-based sunscreens to their guests. “These partnerships have had a tremendous impact raising awareness about this issue,” says founder and CEO Brian Guadagno, who notes that inquiries and sales have increased this year.

As Bluestein notes there are some concerns about this and other potential bans,

“Eliminating the use of sunscreen ingredients considered to be safe and effective by the FDA with a long history of use not only restricts consumer choice, but is also at odds with skin cancer prevention efforts […],” says Bayer, owner of the Coppertone brand, in a statement to Fast Company. Bayer disputes the validity of studies used to support the ban, which were published by scientists from U.S. National Oceanic & Atmospheric Administration, the nonprofit Haereticus Environmental Laboratory, Tel Aviv University, the University of Hawaii, and elsewhere. “Oxybenzone in sunscreen has not been scientifically proven to have an effect on the environment. We take this issue seriously and, along with the industry, have supported additional research to confirm that there is no effect.”

Johnson & Johnson, which markets Neutrogena sunscreens, is taking a similar stance, worrying that “the recent efforts in Hawaii to ban sunscreens that contain oxybenzone may actually adversely affect public health,” according to a company spokesperson. “Science shows that sunscreens are a key factor in preventing skin cancer, and our scientific assessment of the lab studies done to date in Hawaii show the methods were questionable and the data insufficient to draw factual conclusions about any impact on coral reefs.”

Terrified (and rightly so) about anything scaring people away from using sunblock, The American Academy of Dermatology, also opposes Hawaii’s ban. Suzanne M. Olbricht, president of the AADA, has issued a statement that the organization “is concerned that the public’s risk of developing skin cancer could increase due to potential new restrictions in Hawaii that impact access to sunscreens with ingredients necessary for broad-spectrum protection, as well as the potential stigma around sunscreen use that could develop as a result of these restrictions.”

The fact is that there are currently a large number of widely available reef-safe products on the market that provide “full spectrum” protection up to SPF50–meaning they protect against both UVB rays that cause sunburns as well as UVA radiation, which causes deeper skin damage. SPFs higher than 50 are largely a marketing gimmick, say advocates of chemical-free products: According to the Environmental Working Group, properly applied SPF 50 sunscreen blocks 98% of UVB rays; SPF 100 blocks 99%. And a sunscreen lotion’s SPF rating has little to do with its ability to shield skin from UVA rays.

I notice neither Bayer nor Johnson & Johnson nor the American Academy of Dermatology make mention of oxybenzone’s possible role as a hormone disruptor.

Given the importance that coral reefs have to the environment we all share, I’m inclined to support the oxybenzone ban based on that alone. Of course, it’s conceivable that metallic nanoparticles may also have a deleterious effect on coral reefs as their use increases. It’s to be hoped that’s not the case but if it is, then I’ll make my decisions accordingly and hope we have a viable alternative.

As for your sunscreen questions and needs, the Environment Working Group (EWG) has extensive information including a product guide on this page (scroll down to EWG’s Sunscreen Guide) and a discussion of ‘high’ SPF numbers I found useful for my decision-making.

Getting chipped

A January 23, 2018 article by John Converse Townsend for Fast Company highlights the author’s experience of ‘getting chipped’ in Wisconsin (US),

I have an RFID, or radio frequency ID, microchip implanted in my hand. Now with a wave, I can unlock doors, fire off texts, login to my computer, and even make credit card payments.

There are others like me: The majority of employees at the Wisconsin tech company Three Square Market (or 32M) have RFID implants, too. Last summer, with the help of Andy “Gonzo” Whitehead, a local body piercer with 17 years of experience, the company hosted a “chipping party” for employees who’d volunteered to test the technology in the workplace.

“We first presented the concept of being chipped to the employees, thinking we might get a few people interested,” CEO [Chief Executive Officer] Todd Westby, who has implants in both hands, told me. “Literally out of the box, we had 40 people out of close to 90 that were here that said, within 10 minutes, ‘I would like to be chipped.’”

Westby’s left hand can get him into the office, make phone calls, and stores his living will and drivers license information, while the chip in his right hand is using for testing new applications. (The CEO’s entire family is chipped, too.) Other employees said they have bitcoin wallets and photos stored on their devices.

The legendary Gonzo Whitehead was waiting for me when I arrived at Three Square Market HQ, located in quiet River Falls, 40 minutes east of Minneapolis. The minutes leading up to the big moment were a bit nervy, after seeing the size of the needle (it’s huge), but the experience was easier than I could have imagined. The RFID chip is the size of a grain of basmati rice, but the pain wasn’t so bad–comparable to a bee sting, and maybe less so. I experienced a bit of bruising afterward (no bleeding), and today the last remaining mark of trauma is a tiny, fading scar between my thumb and index finger. Unless you were looking for it, the chip resting under my skin is invisible.

Truth is, the applications for RFID implants are pretty cool. But right now, they’re also limited. Without a near-field communication (NFC) writer/reader, which powers on a “passive” RFID chip to write and read information to the device’s memory, an implant isn’t of much use. But that’s mostly a hardware issue. As NFC technology becomes available, which is increasingly everywhere thanks to Samsung Pay and Apple Pay and new contactless “tap-and-go” credit cards, the possibilities become limitless. [emphasis mine]

Health and privacy?

Townsend does cover a few possible downsides to the ‘limitless possibilities’ offered by RFID’s combined with NFC technology,

From a health perspective, the RFID implants are biologically safe–not so different from birth control implants [emphasis mine]. [US Food and Drug Administration] FDA-sanctioned for use in humans since 2004, the chips neither trigger metal detectors nor disrupt [magnetic resonance imaging] MRIs, and their glass casings hold up to pressure testing, whether that’s being dropped from a rooftop or being run over by a pickup truck.

The privacy side of things is a bit more complicated, but the undeniable reality is that privacy isn’t as prized as we’d like to think [emphasis mine]. It’s already a regular concession to convenience.

“Your information’s for sale every day,” McMullen [Patrick McMullen, president, Three Square Market] says. “Thirty-four billion avenues exist for your information to travel down every single day, whether you’re checking Facebook, checking out at the supermarket, driving your car . . . your information’s everywhere.

Townsend may not be fully up-to-date on the subject of birth control implants. I think ‘safeish’ might be a better description in light of this news of almost two years ago (from a March 1, 2016 news item on CBS [Columbia Broadcasting Service] News [online]), Note: Links have been removed,

[US] Federal health regulators plan to warn consumers more strongly about Essure, a contraceptive implant that has drawn thousands of complaints from women reporting chronic pain, bleeding and other health problems.

The Food and Drug Administration announced Monday it would add a boxed warning — its most serious type — to alert doctors and patients to problems reported with the nickel-titanium implant.

But the FDA stopped short of removing the device from the market, a step favored by many women who have petitioned the agency in the last year. Instead, the agency is requiring manufacturer Bayer to conduct studies of the device to further assess its risks in different groups of women.

The FDA is requiring Bayer to conduct a study of 2,000 patients comparing problems like unplanned pregnancy and pelvic pain between patients getting Essure and those receiving traditional “tube tying” surgery. Agency officials said they have reviewed more than 600 reports of women becoming pregnant after receiving Essure. Women are supposed to get a test after three months to make sure Essure is working appropriately, but the agency noted some women do not follow-up for the test.

FDA officials acknowledged the proposed study would take years to complete, but said Bayer would be expected to submit interim results by mid-2017.

According to a Sept. 25, 2017 article by Kerri O’Brien for WRIC.com, Bayer had suspended sales of their device in all countries except the US,

Bayer, the manufacturer of Essure, has announced it’s halting sales of Essure in all countries outside of the U.S. In a statement, Bayer told 8News it’s due to a lack of interest in the product outside of the U.S.

“Bayer made a commercial decision this Spring to discontinue the distribution of Essure® outside of the U.S. where there is not as much patient interest in permanent birth control,” the statement read.

The move also comes after the European Union suspended sales of the device. The suspension was prompted by the National Standards Authority of Ireland declining to renew Essure’s CE marketing. “CE,” according to the European Commission website signifies products sold in the EEA that has been assessed to meet “high safety, health, and environmental protection requirements.”

These excerpts are about the Essure birth control implant. Perhaps others are safer? That noted, it does seem that Townsend was a bit dismissive of safety concerns.

As for privacy, he does investigate further to discover this,

As technology evolves and becomes more sophisticated, the methods to break it also evolve and get more sophisticated, says D.C.-based privacy expert Michelle De Mooy. Even so, McMullen believes that our personal information is safer in our hand than in our wallets. He  says the smartphone you touch 2,500 times a day does 100 times more reporting of data than does an RFID implant, plus the chip can save you from pickpockets and avoid credit card skimmers altogether.

Well, the first sentence suggests some caution. As for De Mooy, there’s this from her profile page on the Center for Democracy and Technology website (Note: A link has been removed),

Michelle De Mooy is Director of the Privacy & Data Project at the Center for Democracy & Technology. She advocates for data privacy rights and protections in legislation and regulation, works closely with industry and other stakeholders to investigate good data practices and controls, as well as identifying and researching emerging technology that impacts personal privacy. She leads CDT’s health privacy work, chairing the Health Privacy Working Group and focusing on the intersection between individual privacy, health information and technology. Michelle’s current research is focused on ethical and privacy-aware internal research and development in wearables, the application of data analytics to health information found on non-traditional platforms, like social media, and the growing market for genetic data. She has testified before Congress on health policy, spoken about native advertising at the Federal Trade Commission, and written about employee wellness programs for US News & World Report’s “Policy Dose” blog. Michelle is a frequent media contributor, appearing in the New York Times, the Guardian, the Wall Street Journal, Vice, and the Los Angeles Times, as well as on The Today Show, Voice of America, and Government Matters TV programs.

Ethics anyone?

Townsend does raise some ethical issues (Note: A link has been removed),

… Word from CEO Todd Westby is that parents in Wisconsin have been asking whether (and when) they can have their children implanted with GPS-enabled devices (which, incidentally, is the subject of the “Arkangel” episode in the new season of Black Mirror [US television programme]). But that, of course, raises ethical questions: What if a kid refused to be chipped? What if they never knew?

Final comments on implanted RFID chips and bodyhacking

It doesn’t seem that implantable chips have changed much since I first wrote about them in a May 27, 2010 posting titled: Researcher infects self with virus.  In that instance, Dr Mark Gasson, a researcher at the University of Reading. introduced a virus into a computer chip implanted in his body.

Of course since 2010, there are additional implantable items such as computer chips and more making their way into our bodies and it doesn’t seem to be much public discussion (other than in popular culture) about the implications.

Presumably, there are policy makers tracking these developments. I have to wonder if the technology gurus will continue to tout these technologies as already here or having made such inroads that we (the public) are presented with a fait accompli with the policy makers following behind.

3D bioprinting: a conference about the latest trends (May 3 – 5, 2017 at the University of British Columbia, Vancouver)

The University of British Columbia’s (UBC) Peter Wall Institute for Advanced Studies (PWIAS) is hosting along with local biotech firm, Aspect Biosystems, a May 3 -5, 2017 international research roundtable known as ‘Printing the Future of Therapeutics in 3D‘.

A May 1, 2017 UBC news release (received via email) offers some insight into the field of bioprinting from one of the roundtable organizers,

This week, global experts will gather [4] at the University of British
Columbia to discuss the latest trends in 3D bioprinting—a technology
used to create living tissues and organs.

In this Q&A, UBC chemical and biological engineering professor
Vikramaditya Yadav [5], who is also with the Regenerative Medicine
Cluster Initiative in B.C., explains how bioprinting could potentially
transform healthcare and drug development, and highlights Canadian
innovations in this field.

WHY IS 3D BIOPRINTING SIGNIFICANT?

Bioprinted tissues or organs could allow scientists to predict
beforehand how a drug will interact within the body. For every
life-saving therapeutic drug that makes its way into our medicine
cabinets, Health Canada blocks the entry of nine drugs because they are
proven unsafe or ineffective. Eliminating poor-quality drug candidates
to reduce development costs—and therefore the cost to consumers—has
never been more urgent.

In Canada alone, nearly 4,500 individuals are waiting to be matched with
organ donors. If and when bioprinters evolve to the point where they can
manufacture implantable organs, the concept of an organ transplant
waiting list would cease to exist. And bioprinted tissues and organs
from a patient’s own healthy cells could potentially reduce the risk
of transplant rejection and related challenges.

HOW IS THIS TECHNOLOGY CURRENTLY BEING USED?

Skin, cartilage and bone, and blood vessels are some of the tissue types
that have been successfully constructed using bioprinting. Two of the
most active players are the Wake Forest Institute for Regenerative
Medicine in North Carolina, which reports that its bioprinters can make
enough replacement skin to cover a burn with 10 times less healthy
tissue than is usually needed, and California-based Organovo, which
makes its kidney and liver tissue commercially available to
pharmaceutical companies for drug testing.

Beyond medicine, bioprinting has already been commercialized to print
meat and artificial leather. It’s been estimated that the global
bioprinting market will hit $2 billion by 2021.

HOW IS CANADA INVOLVED IN THIS FIELD?

Canada is home to some of the most innovative research clusters and
start-up companies in the field. The UBC spin-off Aspect Biosystems [6]
has pioneered a bioprinting paradigm that rapidly prints on-demand
tissues. It has successfully generated tissues found in human lungs.

Many initiatives at Canadian universities are laying strong foundations
for the translation of bioprinting and tissue engineering into
mainstream medical technologies. These include the Regenerative Medicine
Cluster Initiative in B.C., which is headed by UBC, and the University
of Toronto’s Institute of Biomaterials and Biomedical Engineering.

WHAT ETHICAL ISSUES DOES BIOPRINTING CREATE?

There are concerns about the quality of the printed tissues. It’s
important to note that the U.S. Food and Drug Administration and Health
Canada are dedicating entire divisions to regulation of biomanufactured
products and biomedical devices, and the FDA also has a special division
that focuses on regulation of additive manufacturing – another name
for 3D printing.

These regulatory bodies have an impressive track record that should
assuage concerns about the marketing of substandard tissue. But cost and
pricing are arguably much more complex issues.

Some ethicists have also raised questions about whether society is not
too far away from creating Replicants, à la _Blade Runner_. The idea is
fascinating, scary and ethically grey. In theory, if one could replace
the extracellular matrix of bones and muscles with a stronger substitute
and use cells that are viable for longer, it is not too far-fetched to
create bones or muscles that are stronger and more durable than their
natural counterparts.

WILL DOCTORS BE PRINTING REPLACEMENT BODY PARTS IN 20 YEARS’ TIME?

This is still some way off. Optimistically, patients could see the
technology in certain clinical environments within the next decade.
However, some technical challenges must be addressed in order for this
to occur, beginning with faithful replication of the correct 3D
architecture and vascularity of tissues and organs. The bioprinters
themselves need to be improved in order to increase cell viability after
printing.

These developments are happening as we speak. Regulation, though, will
be the biggest challenge for the field in the coming years.

There are some events open to the public (from the international research roundtable homepage),

OPEN EVENTS

You’re invited to attend the open events associated with Printing the Future of Therapeutics in 3D.

Café Scientifique

Thursday, May 4, 2017
Telus World of Science
5:30 – 8:00pm [all tickets have been claimed as of May 2, 2017 at 3:15 pm PT]

3D Bioprinting: Shaping the Future of Health

Imagine a world where drugs are developed without the use of animals, where doctors know how a patient will react to a drug before prescribing it and where patients can have a replacement organ 3D-printed using their own cells, without dealing with long donor waiting lists or organ rejection. 3D bioprinting could enable this world. Join us for lively discussion and dessert as experts in the field discuss the exciting potential of 3D bioprinting and the ethical issues raised when you can print human tissues on demand. This is also a rare opportunity to see a bioprinter live in action!

Open Session

Friday, May 5, 2017
Peter Wall Institute for Advanced Studies
2:00 – 7:00pm

A Scientific Discussion on the Promise of 3D Bioprinting

The medical industry is struggling to keep our ageing population healthy. Developing effective and safe drugs is too expensive and time-consuming to continue unchanged. We cannot meet the current demand for transplant organs, and people are dying on the donor waiting list every day.  We invite you to join an open session where four of the most influential academic and industry professionals in the field discuss how 3D bioprinting is being used to shape the future of health and what ethical challenges may be involved if you are able to print your own organs.

ROUNDTABLE INFORMATION

The University of British Columbia and the award-winning bioprinting company Aspect Biosystems, are proud to be co-organizing the first “Printing the Future of Therapeutics in 3D” International Research Roundtable. This event will congregate global leaders in tissue engineering research and pharmaceutical industry experts to discuss the rapidly emerging and potentially game-changing technology of 3D-printing living human tissues (bioprinting). The goals are to:

Highlight the state-of-the-art in 3D bioprinting research
Ideate on disruptive innovations that will transform bioprinting from a novel research tool to a broadly adopted systematic practice
Formulate an actionable strategy for industry engagement, clinical translation and societal impact
Present in a public forum, key messages to educate and stimulate discussion on the promises of bioprinting technology

The Roundtable will bring together a unique collection of industry experts and academic leaders to define a guiding vision to efficiently deploy bioprinting technology for the discovery and development of new therapeutics. As the novel technology of 3D bioprinting is more broadly adopted, we envision this Roundtable will become a key annual meeting to help guide the development of the technology both in Canada and globally.

We thank you for your involvement in this ground-breaking event and look forward to you all joining us in Vancouver for this unique research roundtable.

Kind Regards,
The Organizing Committee
Christian Naus, Professor, Cellular & Physiological Sciences, UBC
Vikram Yadav, Assistant Professor, Chemical & Biological Engineering, UBC
Tamer Mohamed, CEO, Aspect Biosystems
Sam Wadsworth, CSO, Aspect Biosystems
Natalie Korenic, Business Coordinator, Aspect Biosystems

I’m glad to see this event is taking place—and with public events too! (Wish I’d seen the Café Scientifique announcement earlier when I first checked for tickets  yesterday. I was hoping there’d been some cancellations today.) Finally, for the interested, you can find Aspect Biosystems here.

New iron oxide nanoparticle as an MRI (magnetic resonance imaging) contrast agent

This high-resolution transmission electron micrograph of particles made by the research team shows the particles’ highly uniform size and shape. These are iron oxide particles just 3 nanometers across, coated with a zwitterion layer. Their small size means they can easily be cleared through the kidneys after injection. Courtesy of the researchers

A Feb. 14, 2017 news item on ScienceDaily announces a new MRI (magnetic resonance imaging) contrast agent,

A new, specially coated iron oxide nanoparticle developed by a team at MIT [Massachusetts Institute of Technology] and elsewhere could provide an alternative to conventional gadolinium-based contrast agents used for magnetic resonance imaging (MRI) procedures. In rare cases, the currently used gadolinium agents have been found to produce adverse effects in patients with impaired kidney function.

A Feb. 14, 2017 MIT news release (also on EurekAlert), which originated the news item, provides more technical detail,

 

The advent of MRI technology, which is used to observe details of specific organs or blood vessels, has been an enormous boon to medical diagnostics over the last few decades. About a third of the 60 million MRI procedures done annually worldwide use contrast-enhancing agents, mostly containing the element gadolinium. While these contrast agents have mostly proven safe over many years of use, some rare but significant side effects have shown up in a very small subset of patients. There may soon be a safer substitute thanks to this new research.

In place of gadolinium-based contrast agents, the researchers have found that they can produce similar MRI contrast with tiny nanoparticles of iron oxide that have been treated with a zwitterion coating. (Zwitterions are molecules that have areas of both positive and negative electrical charges, which cancel out to make them neutral overall.) The findings are being published this week in the Proceedings of the National Academy of Sciences, in a paper by Moungi Bawendi, the Lester Wolfe Professor of Chemistry at MIT; He Wei, an MIT postdoc; Oliver Bruns, an MIT research scientist; Michael Kaul at the University Medical Center Hamburg-Eppendorf in Germany; and 15 others.

Contrast agents, injected into the patient during an MRI procedure and designed to be quickly cleared from the body by the kidneys afterwards, are needed to make fine details of organ structures, blood vessels, and other specific tissues clearly visible in the images. Some agents produce dark areas in the resulting image, while others produce light areas. The primary agents for producing light areas contain gadolinium.

Iron oxide particles have been largely used as negative (dark) contrast agents, but radiologists vastly prefer positive (light) contrast agents such as gadolinium-based agents, as negative contrast can sometimes be difficult to distinguish from certain imaging artifacts and internal bleeding. But while the gadolinium-based agents have become the standard, evidence shows that in some very rare cases they can lead to an untreatable condition called nephrogenic systemic fibrosis, which can be fatal. In addition, evidence now shows that the gadolinium can build up in the brain, and although no effects of this buildup have yet been demonstrated, the FDA is investigating it for potential harm.

“Over the last decade, more and more side effects have come to light” from the gadolinium agents, Bruns says, so that led the research team to search for alternatives. “None of these issues exist for iron oxide,” at least none that have yet been detected, he says.

The key new finding by this team was to combine two existing techniques: making very tiny particles of iron oxide, and attaching certain molecules (called surface ligands) to the outsides of these particles to optimize their characteristics. The iron oxide inorganic core is small enough to produce a pronounced positive contrast in MRI, and the zwitterionic surface ligand, which was recently developed by Wei and coworkers in the Bawendi research group, makes the iron oxide particles water-soluble, compact, and biocompatible.

The combination of a very tiny iron oxide core and an ultrathin ligand shell leads to a total hydrodynamic diameter of 4.7 nanometers, below the 5.5-nanometer renal clearance threshold. This means that the coated iron oxide should quickly clear through the kidneys and not accumulate. This renal clearance property is an important feature where the particles perform comparably to gadolinium-based contrast agents.

Now that initial tests have demonstrated the particles’ effectiveness as contrast agents, Wei and Bruns say the next step will be to do further toxicology testing to show the particles’ safety, and to continue to improve the characteristics of the material. “It’s not perfect. We have more work to do,” Bruns says. But because iron oxide has been used for so long and in so many ways, even as an iron supplement, any negative effects could likely be treated by well-established protocols, the researchers say. If all goes well, the team is considering setting up a startup company to bring the material to production.

For some patients who are currently excluded from getting MRIs because of potential side effects of gadolinium, the new agents “could allow those patients to be eligible again” for the procedure, Bruns says. And, if it does turn out that the accumulation of gadolinium in the brain has negative effects, an overall phase-out of gadolinium for such uses could be needed. “If that turned out to be the case, this could potentially be a complete replacement,” he says.

Ralph Weissleder, a physician at Massachusetts General Hospital who was not involved in this work, says, “The work is of high interest, given the limitations of gadolinium-based contrast agents, which typically have short vascular half-lives and may be contraindicated in renally compromised patients.”

The research team included researchers in MIT’s chemistry, biological engineering, nuclear science and engineering, brain and cognitive sciences, and materials science and engineering departments and its program in Health Sciences and Technology; and at the University Medical Center Hamburg-Eppendorf; Brown University; and the Massachusetts General Hospital. It was supported by the MIT-Harvard NIH Center for Cancer Nanotechnology, the Army Research Office through MIT’s Institute for Soldier Nanotechnologies, the NIH-funded Laser Biomedical Research Center, the MIT Deshpande Center, and the European Union Seventh Framework Program.

Here’s a link to and a citation for the paper,

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents by He Wei, Oliver T. Bruns, Michael G. Kaul, Eric C. Hansen, Mariya Barch, Agata Wiśniowsk, Ou Chen, Yue Chen, Nan Li, Satoshi Okada, Jose M. Cordero, Markus Heine, Christian T. Farrar, Daniel M. Montana, Gerhard Adam, Harald Ittrich, Alan Jasanoff, Peter Nielsen, and Moungi G. Bawendi. PNAS February 13, 2017 doi: 10.1073/pnas.1620145114 Published online before print February 13, 2017

This paper is behind a paywall.

Nanoparticles in baby formula

Needle-like particles of hydroxyapatite found in infant formula by ASU researchers. Westerhoff and Schoepf/ASU, CC BY-ND

Needle-like particles of hydroxyapatite found in infant formula by ASU [Arizona State University] researchers. Westerhoff and Schoepf/ASU, CC BY-ND

Nanowerk is featuring an essay about hydroxyapatite nanoparticles in baby formula written by Dr. Andrew Maynard in a May 17, 2016 news item (Note: A link has been removed),

There’s a lot of stuff you’d expect to find in baby formula: proteins, carbs, vitamins, essential minerals. But parents probably wouldn’t anticipate finding extremely small, needle-like particles. Yet this is exactly what a team of scientists here at Arizona State University [ASU] recently discovered.

The research, commissioned and published by Friends of the Earth (FoE) – an environmental advocacy group – analyzed six commonly available off-the-shelf baby formulas (liquid and powder) and found nanometer-scale needle-like particles in three of them. The particles were made of hydroxyapatite – a poorly soluble calcium-rich mineral. Manufacturers use it to regulate acidity in some foods, and it’s also available as a dietary supplement.

Andrew’s May 17, 2016 essay first appeared on The Conversation website,

Looking at these particles at super-high magnification, it’s hard not to feel a little anxious about feeding them to a baby. They appear sharp and dangerous – not the sort of thing that has any place around infants. …

… questions like “should infants be ingesting them?” make a lot of sense. However, as is so often the case, the answers are not quite so straightforward.

Andrew begins by explaining about calcium and hydroxyapatite (from The Conversation),

Calcium is an essential part of a growing infant’s diet, and is a legally required component in formula. But not necessarily in the form of hydroxyapatite nanoparticles.

Hydroxyapatite is a tough, durable mineral. It’s naturally made in our bodies as an essential part of bones and teeth – it’s what makes them so strong. So it’s tempting to assume the substance is safe to eat. But just because our bones and teeth are made of the mineral doesn’t automatically make it safe to ingest outright.

The issue here is what the hydroxyapatite in formula might do before it’s digested, dissolved and reconstituted inside babies’ bodies. The size and shape of the particles ingested has a lot to do with how they behave within a living system.

He then discusses size and shape, which are important at the nanoscale,

Size and shape can make a difference between safe and unsafe when it comes to particles in our food. Small particles aren’t necessarily bad. But they can potentially get to parts of our body that larger ones can’t reach. Think through the gut wall, into the bloodstream, and into organs and cells. Ingested nanoscale particles may be able to interfere with cells – even beneficial gut microbes – in ways that larger particles don’t.

These possibilities don’t necessarily make nanoparticles harmful. Our bodies are pretty well adapted to handling naturally occurring nanoscale particles – you probably ate some last time you had burnt toast (carbon nanoparticles), or poorly washed vegetables (clay nanoparticles from the soil). And of course, how much of a material we’re exposed to is at least as important as how potentially hazardous it is.

Yet there’s a lot we still don’t know about the safety of intentionally engineered nanoparticles in food. Toxicologists have started paying close attention to such particles, just in case their tiny size makes them more harmful than otherwise expected.

Currently, hydroxyapatite is considered safe at the macroscale by the US Food and Drug Administration (FDA). However, the agency has indicated that nanoscale versions of safe materials such as hydroxyapatite may not be safe food additives. From Andrew’s May 17, 2016 essay,

Hydroxyapatite is a tough, durable mineral. It’s naturally made in our bodies as an essential part of bones and teeth – it’s what makes them so strong. So it’s tempting to assume the substance is safe to eat. But just because our bones and teeth are made of the mineral doesn’t automatically make it safe to ingest outright.

The issue here is what the hydroxyapatite in formula might do before it’s digested, dissolved and reconstituted inside babies’ bodies. The size and shape of the particles ingested has a lot to do with how they behave within a living system. Size and shape can make a difference between safe and unsafe when it comes to particles in our food. Small particles aren’t necessarily bad. But they can potentially get to parts of our body that larger ones can’t reach. Think through the gut wall, into the bloodstream, and into organs and cells. Ingested nanoscale particles may be able to interfere with cells – even beneficial gut microbes – in ways that larger particles don’t.These possibilities don’t necessarily make nanoparticles harmful. Our bodies are pretty well adapted to handling naturally occurring nanoscale particles – you probably ate some last time you had burnt toast (carbon nanoparticles), or poorly washed vegetables (clay nanoparticles from the soil). And of course, how much of a material we’re exposed to is at least as important as how potentially hazardous it is.Yet there’s a lot we still don’t know about the safety of intentionally engineered nanoparticles in food. Toxicologists have started paying close attention to such particles, just in case their tiny size makes them more harmful than otherwise expected.

Putting particle size to one side for a moment, hydroxyapatite is classified by the US Food and Drug Administration (FDA) as “Generally Regarded As Safe.” That means it considers the material safe for use in food products – at least in a non-nano form. However, the agency has raised concerns that nanoscale versions of food ingredients may not be as safe as their larger counterparts.Some manufacturers may be interested in the potential benefits of “nanosizing” – such as increasing the uptake of vitamins and minerals, or altering the physical, textural and sensory properties of foods. But because decreasing particle size may also affect product safety, the FDA indicates that intentionally nanosizing already regulated food ingredients could require regulatory reevaluation.In other words, even though non-nanoscale hydroxyapatite is “Generally Regarded As Safe,” according to the FDA, the safety of any nanoscale form of the substance would need to be reevaluated before being added to food products.Despite this size-safety relationship, the FDA confirmed to me that the agency is unaware of any food substance intentionally engineered at the nanoscale that has enough generally available safety data to determine it should be “Generally Regarded As Safe.”Casting further uncertainty on the use of nanoscale hydroxyapatite in food, a 2015 report from the European Scientific Committee on Consumer Safety (SCCS) suggests there may be some cause for concern when it comes to this particular nanomaterial.Prompted by the use of nanoscale hydroxyapatite in dental products to strengthen teeth (which they consider “cosmetic products”), the SCCS reviewed published research on the material’s potential to cause harm. Their conclusion?

The available information indicates that nano-hydroxyapatite in needle-shaped form is of concern in relation to potential toxicity. Therefore, needle-shaped nano-hydroxyapatite should not be used in cosmetic products.

This recommendation was based on a handful of studies, none of which involved exposing people to the substance. Researchers injected hydroxyapatite needles directly into the bloodstream of rats. Others exposed cells outside the body to the material and observed the effects. In each case, there were tantalizing hints that the small particles interfered in some way with normal biological functions. But the results were insufficient to indicate whether the effects were meaningful in people.

As Andrew also notes in his essay, none of the studies examined by the SCCS OEuropean Scientific Committee on Consumer Safety) looked at what happens to nano-hydroxyapatite once it enters your gut and that is what the researchers at Arizona State University were considering (from the May 17, 2016 essay),

The good news is that, according to preliminary studies from ASU researchers, hydroxyapatite needles don’t last long in the digestive system.

This research is still being reviewed for publication. But early indications are that as soon as the needle-like nanoparticles hit the highly acidic fluid in the stomach, they begin to dissolve. So fast in fact, that by the time they leave the stomach – an exceedingly hostile environment – they are no longer the nanoparticles they started out as.

These findings make sense since we know hydroxyapatite dissolves in acids, and small particles typically dissolve faster than larger ones. So maybe nanoscale hydroxyapatite needles in food are safer than they sound.

This doesn’t mean that the nano-needles are completely off the hook, as some of them may get past the stomach intact and reach more vulnerable parts of the gut. But the findings do suggest these ultra-small needle-like particles could be an effective source of dietary calcium – possibly more so than larger or less needle-like particles that may not dissolve as quickly.

Intriguingly, recent research has indicated that calcium phosphate nanoparticles form naturally in our stomachs and go on to be an important part of our immune system. It’s possible that rapidly dissolving hydroxyapatite nano-needles are actually a boon, providing raw material for these natural and essential nanoparticles.

While it’s comforting to know that preliminary research suggests that the hydroxyapatite nanoparticles are likely safe for use in food products, Andrew points out that more needs to be done to insure safety (from the May 17, 2016 essay),

And yet, even if these needle-like hydroxyapatite nanoparticles in infant formula are ultimately a good thing, the FoE report raises a number of unresolved questions. Did the manufacturers knowingly add the nanoparticles to their products? How are they and the FDA ensuring the products’ safety? Do consumers have a right to know when they’re feeding their babies nanoparticles?

Whether the manufacturers knowingly added these particles to their formula is not clear. At this point, it’s not even clear why they might have been added, as hydroxyapatite does not appear to be a substantial source of calcium in most formula. …

And regardless of the benefits and risks of nanoparticles in infant formula, parents have a right to know what’s in the products they’re feeding their children. In Europe, food ingredients must be legally labeled if they are nanoscale. In the U.S., there is no such requirement, leaving American parents to feel somewhat left in the dark by producers, the FDA and policy makers.

As far as I’m aware, the Canadian situation is much the same as the US. If the material is considered safe at the macroscale, there is no requirement to indicate that a nanoscale version of the material is in the product.

I encourage you to read Andrew’s essay in its entirety. As for the FoE report (Nanoparticles in baby formula: Tiny new ingredients are a big concern), that is here.

AquAdvantage salmon (genetically modified) approved for consumption in Canada

This is an update of the AquAdvantage salmon story covered in my Dec. 4, 2015 post (scroll down about 40% of the way). At the time, the US Food and Drug Administration (FDA) had just given approval for consumption of the fish. There was speculation there would be a long hard fight over approval in Canada. This does not seem to have been the case, according to a May 10, 2016 news item announcing Health Canada’s on phys.org,

Canada’s health ministry on Thursday [May 19, 2016] approved a type of genetically modified salmon as safe to eat, making it the first transgenic animal destined for Canadian dinner tables.

This comes six months after US authorities gave the green light to sell the fish in American grocery stores.

The decisions by Health Canada and the US Food and Drug Administration follow two decades of controversy over the fish, which is an Atlantic salmon injected with genes from Pacific Chinook salmon and a fish known as the ocean pout to make it grow faster.

The resulting fish, called AquAdvantage Salmon, is made by AquaBounty Technologies in Massachusetts, and can reach adult size in 16 to 18 months instead of 30 months for normal Atlantic salmon.

A May 19, 2016 BIOTECanada news release on businesswire provides more detail about one of the salmon’s Canadian connections,

Canadian technology emanating from Memorial University developed the AquAdvantage salmon by introducing a growth hormone gene from Chinook salmon into the genome of Atlantic salmon. This results in a salmon which grows faster and reaches market size quicker and AquAdvantage salmon is identical to other farmed salmon. The AquAdvantage salmon also received US FDA approval in November 2015. With the growing world population, AquaBounty is one of many biotechnology companies offering safe and sustainable means to enhance the security and supply of food in the world. AquaBounty has improved the productivity of aquaculture through its use of biotechnology and modern breeding technics that have led to the development of AquAdvantage salmon.

“Importantly, today’s approval is a result of a four year science-based regulatory approval process which involved four federal government departments including Agriculture and AgriFood, Canada Food Inspection Agency, Environment and Climate Change, Fisheries and Oceans and Health which demonstrates the rigour and scope of science based regulatory approvals in Canada. Coupled with the report from the [US] National Academy of Sciences today’s [May 19, 2016] approval clearly demonstrates that genetic engineering of food is not only necessary but also extremely safe,” concluded Casey [Andrew Casey, President and CEO BIOTECanada].

There’s another connection, the salmon hatcheries are based in Prince Edward Island.

While BIOTECanada’s Andrew Casey is crowing about this approval, it should be noted that there was a losing court battle with British Columbia’s Living Oceans Society and Nova Scotia’s Ecology Action Centre both challenging the federal government’s approval. They may have lost *the* battle but, as the cliché goes, ‘the war is not over yet’. There’s an Issue about the lack of labeling and there’s always the  possibility that retailers and/or consumers may decide to boycott the fish.

As for BIOTECanada, there’s this description from the news release,

BIOTECanada is the national industry association with more than 230 members reflecting the diverse nature of Canada’s health, industrial and agricultural biotechnology sectors. In addition to providing significant health benefits for Canadians, the biotechnology industry has quickly become an essential part of the transformation of many traditional cornerstones of the Canadian economy including manufacturing, automotive, energy, aerospace and forestry industries. Biotechnology in all of its applications from health, agriculture and industrial is offering solutions for the collective population.

You can find the BIOTECanada website here.

Personally, I’m a bit ambivalent about it all. I understand the necessity for changing our food production processes but I do think more attention should be paid to consumers’ concerns and that organizations such as BIOTECanada could do a better job of communicating.

*’the’ added on Aug. 4, 2016.

Opioid addiction and nanotechnology in Pennsylvania, US

Combating a drug addiction ‘crisis’ with a nanotechnology-enabled solution is the main topic although the technology is being implemented for another problem first according to this May 4, 2016 article by John Luciew for pennlive.com (Note: Links have been removed),

Treating pain is a constant in medicine. It’s part of the human condition, known as the “fifth vital sign” among physicians. Effectively treating pain will continue to play a central role in medicine, despite the societal shock waves brought on by the rapid rise in opioid addiction across America.

The fallout from our nation’s opioid addiction crisis is roiling the medical and pharmaceutical industries, where regulatory action is rapidly reining in opioid painkiller prescriptions with new guidelines and stricter controls.

By harnessing nanotechnology and small-particles physics, Iroko Pharmaceuticals is developing a new class of low-dose prescription painkillers. Company executives say their line of nonsteroidal anti-inflammatory drugs could be the opioid alternative that the medical community has been looking for amid America’s addiction crisis.

The pharmaceutical company is Pennsylvania-based (US) and it isn’t tackling the ‘opioid addiction crisis’ yet. First, there’s this,

Its new line of prescription painkillers are predicated upon a highly patented process of pulverizing drug molecules so they are up to 100 times smaller, which markedly increases their pain-killing effectiveness at dramatically lower doses.

Right now, Iroko is focusing this nanotechnology on creating a full line of low-dose prescription painkillers based upon the class of drugs known as nonsteroidal anti-inflammatories, or NSAIDs. There are six NSAID molecules, the most common being Ibuprofen. Iroko is planning nanotechnology technology versions for all six NSAID molecules, three of which have already received approval from the Food and Drug Administration.

Luciew has done some homework on the technology,

“We solved a chemistry problem by using physics,” explained Iroko Chairman Osagie Imasogie, who founded the company [Iroko Pharmaceuticals] in 2007.

Yet, the company that actually solved the physics problem was iCeutica, founded in Australia and now based in King of Prussia, Pa.

iCeutica owns the patented SoluMatrix fine particle process that pulverizes drug molecules into nano-sized particles, enabling low doses of a drug to be better absorbed by the body, thus providing faster and far more effective pain relief.

Of course, the practice of crushing and grinding drug powders is as old as the pharmacist’s mortar and pestle. But there’s never been a way of pulverizing a drug molecule into nano particles that was scalable for industrial production — not until iCeutica created its SoluMatrix process, that is.

iCeutica provides a description of the technology on its SoluMatrix webpage,

iCeutica’s proprietary SoluMatrix™ Fine Particle Technology fuels new product development and solves problems of bioavailability, variability, side effects and delivery of marketed or development-stage pharmaceuticals.

The SoluMatrix technology is a scaleable and cost-effective manufacturing process that can produce submicron-sized drug particles that are 10 to 200 times smaller than conventional drug particles. The particles generated using this technology, which both grinds the drug particles into a superfine powder and protects those submicron particles from subsequent agglomeration (or clumping together into big particles), comprise a single unit operation and can be manufactured into tablets, capsules and other dosage forms without further processing.

The SoluMatrix technology improves the performance of pharmaceuticals by dramatically changing how the drug dissolves and is absorbed. By making submicron-sized particles of a drug, it is possible to:

Unfortunately there aren’t more details. I’m somewhat puzzled  by the submicron measurement why not state the size using the term nanometre?

Getting back  to Iroko, Imasogie, impressed with the SoluMatrix technology, has made a major investment in iCeutica and is chair of iCeutica’s board. His homebase company, Iroko holds exclusive global rights to SoluMatrix.

Luciew’s article describes the current situation in the NSAID market,

Iroko officials acknowledge that NSAID painkillers carry their own health risks, including the potential for stomach ulcers, kidney problems and cardio-vascular ailments, up to and including stroke and heart attack. The fears associated with NSAIDs peaked a decade ago with the Vioxx case, a popular prescription NSAID that was eventually taken off the market due to associated cardiac and other risks.

The latest FDA guidelines for NSAID use calls for the lowest effective dose, which precisely describes the nanotechnology-driven low-dose NSAID drugs Iroko is rolling out. What is more, due to the ongoing opioid crisis, both the FDA and the Centers for Disease Control are heavily emphasizing non-opioid alternatives for pain relief, further opening to door for Iroko’s pain products.

That said about the issues with NSAIDs, Luciew outlines Iroko’s current offerings and explains what makes this technology so attractive,

According to Imasogie, Iroko’s line of low-dose, nanotechnology NSAIDs fits both sets of regulatory safety criteria. The new drugs are the lowest effective dose for NSAIDs, and are a viable pain-killing alternative to opioids, especially when it comes to treating osteoarthritis and other moderate pain.

“No one is going to give an NSAID if you have cancer,” Imasogie says. “But for chronic low back pain, yes.”

Three of Iroko’s six low-dose NSAID offerings have already received FDA approval and are on the market:

  • Zorvolex (diclofenac), approved in October 2013 for the management of mild to moderate acute pain in adults and in August 2014 for the management of osteoarthritis pain.
  • Tivorbex, approved in February 2014 for treatment of mild to moderate acute pain in adults.
  • Vivlodex, approved in October 2015 as another option for treatment of osteoarthritis pain. Three more of Iroko’s low-dose NSAIDs are awaiting approval.

These nano drugs are effective at doses of 35 to 40 milligrams to as low as 10 milligrams, the company says. That’s compared to other NSAID doses that start at 200 milligrams. As a result, Iroko’s low-dose NSAID drugs are being marketed as providing a prescription alternative to opioids at the precise moment everyone from the White House to the white-coat-clad family physician is searching for one.

If you the have time and interest, I encourage you to read Luciew’s article in its entirety. He covers more market issues and includes an enbedded video in his piece.

One last note about Iroko Pharmaceuticals, the company is named after a tree found on the African continent and executives of the company have hinted they are experimenting with SoluMatrix to make low-dose opioids available in the future.

While I have my doubts about the opioid addiction ‘crisis’, I do believe that lower, more effective doses of painkillers, regardless of their drug class, can only benefit patients.

Chip in brain lets quadriplegic (tetraplegic) move hands and fingers

An April 13, 2016 news item on ScienceDaily describes the latest brain implant,

Six years ago, he was paralyzed in a diving accident. Today, he participates in clinical sessions during which he can grasp and swipe a credit card or play a guitar video game with his own fingers and hand. These complex functional movements are driven by his own thoughts and a prototype medical system that are detailed in a study published online today in the journal Nature.

The device, called NeuroLife, was invented at Battelle, which teamed with physicians and neuroscientists from The Ohio State University Wexner Medical Center to develop the research approach and perform the clinical study. Ohio State doctors identified the study participant and implanted a tiny computer chip into his brain.

An April 13, 2016 Ohio State University news release on EurekAlert, which originated the news item, provides more details about the participant and the technology,

That pioneering participant, Ian Burkhart, is a 24-year-old quadriplegic from Dublin, Ohio, and the first person to use this technology. This electronic neural bypass for spinal cord injuries reconnects the brain directly to muscles, allowing voluntary and functional control of a paralyzed limb by using his thoughts. The device interprets thoughts and brain signals then bypasses his injured spinal cord and connects directly to a sleeve that stimulates the muscles that control his arm and hand.

“We’re showing for the first time that a quadriplegic patient is able to improve his level of motor function and hand movements,” said Dr. Ali Rezai, a co-author of the study and a neurosurgeon at Ohio State’s Wexner Medical Center.

Burkhart first demonstrated the neural bypass technology in June 2014, when he was able to open and close his hand simply by thinking about it. Now, he can perform more sophisticated movements with his hands and fingers such as picking up a spoon or picking up and holding a phone to his ear — things he couldn’t do before and which can significantly improve his quality of life.

“It’s amazing to see what he’s accomplished,” said Nick Annetta, electrical engineering lead for Battelle’s team on the project. “Ian can grasp a bottle, pour the contents of the bottle into a jar and put the bottle back down. Then he takes a stir bar, grips that and then stirs the contents of the jar that he just poured and puts it back down. He’s controlling it every step of the way.”

The neural bypass technology combines algorithms that learn and decode the user’s brain activity and a high-definition muscle stimulation sleeve that translates neural impulses from the brain and transmits new signals to the paralyzed limb.

The Battelle team has been working on this technology for more than a decade. To develop the algorithms, software and stimulation sleeve, Battelle scientists first recorded neural impulses from an electrode array implanted in a paralyzed person’s brain. They used that recorded data to illustrate the device’s effect on the patient and prove the concept.

Four years ago, former Battelle researcher Chad Bouton and his team began collaborating with Ohio State Neurological Institute researchers and clinicians Rezai and Dr. Jerry Mysiw to design the clinical trials and validate the feasibility of using the neural bypass technology in patients.

“In the 30 years I’ve been in this field, this is the first time we’ve been able to offer realistic hope to people who have very challenging lives,” said Mysiw, chair of the Department of Physical Medicine and Rehabilitation at Ohio State. “What we’re looking to do is help these people regain more control over their bodies.”

During a three-hour surgery in April 2014, Rezai implanted a computer chip smaller than a pea onto the motor cortex of Burkhart’s brain.

The Ohio State and Battelle teams worked together to figure out the correct sequence of electrodes to stimulate to allow Burkhart to move his fingers and hand functionally. For example, Burkhart uses different brain signals and muscles to rotate his hand, make a fist or pinch his fingers together to grasp an object. As part of the study, Burkhart worked for months using the electrode sleeve to stimulate his forearm to rebuild his atrophied muscles so they would be more responsive to the electric stimulation.

“During the last decade, we’ve learned how to decipher brain signals in patients who are completely paralyzed and now, for the first time, those thoughts are being turned into movement,” said study co-author Bouton, who directed Battelle’s team before he joined the New York-based Feinstein Institute for Medical Research. “Our findings show that signals recorded from within the brain can be re-routed around an injury to the spinal cord, allowing restoration of functional movement and even movement of individual fingers.”

Burkhart said it was an easy decision to participate in the FDA-approved clinical trial at Ohio State’s Wexner Medical Center because he wanted to try to help others with spinal cord injuries. “I just kind of think that it’s my obligation to society,” Burkhart said. “If someone else had an opportunity to do it in some other part of the world, I would hope that they would commit their time so that everyone can benefit from it in the future.”

Rezai and the team from Battelle agree that this technology holds the promise to help patients affected by various brain and spinal cord injuries such as strokes and traumatic brain injury to be more independent and functional.

“We’re hoping that this technology will evolve into a wireless system connecting brain signals and thoughts to the outside world to improve the function and quality of life for those with disabilities,” Rezai said. “One of our major goals is to make this readily available to be used by patients at home.”

Burkhart is the first of a potential five participants in a clinical study. Mysiw and Rezai have identified a second patient who is scheduled to start the study in the summer.

“Participating in this research has changed me in the sense that I have a lot more hope for the future now,” Burkhart said. “I always did have a certain level of hope, but now I know, first-hand, that there are going to be improvements in science and technology that will make my life better.”

Here’s a link to and a citation for the paper,

Restoring cortical control of functional movement in a human with quadriplegia by Chad E. Bouton, Ammar Shaikhouni, Nicholas V. Annetta, Marcia A. Bockbrader, David A. Friedenberg, Dylan M. Nielson, Gaurav Sharma, Per B. Sederberg, Bradley C. Glenn, W. Jerry Mysiw, Austin G. Morgan, Milind Deogaonkar, & Ali R. Rezai. Nature (2016)  doi:10.1038/nature17435 Published online 13 April 2016

This paper is behind a paywall but there is an in depth April 13, 2016 article by Linda Geddes in Nature providing nuggets of new insight such as this,

Previous studies have suggested that after spinal-cord injuries, the brain undergoes ‘reorganization’ — a rewiring of its connections. But this new work suggests that the degree of reorganization occurring after such injuries may be less than previously assumed. “It gives us a lot of hope that there are perhaps not as many neural changes in the brain as we might have imagined [emphasis mine] after an injury like this, and we can bypass damaged areas of the spinal cord to regain movement,” says Bouton.

The Geddes article is open access.

Finally, there’s an April 13, 2016 article by Will Oremus for Slate.com, which notes that this story is not a fairy tale as there’s a possibility the chip will be removed in the near future as the US Food and Drug Administration’s approval of the device was conditional due to this,

Burkhart knows the device was never meant to last forever. The brain implant’s efficacy gradually degrades over time due to scarring in the brain tissue, and eventually that hardware degradation will start to undo the progress that Burkhart and the software have made together.

He told me he has accepted that his newfound mobility is temporary, and that the progress he has made is likely to benefit posterity more than it benefits him. “I now know that when I’m connected to the system I can do all these great things. It won’t be too much of a shock to me [when it’s over], because even now I can only use the system for a few hours a week when I’m down in the lab. But it will be something I’ll certainly miss.”